Blood is a liquid tissue that includes red cells, white cells, corpuscles, and platelets dispersed in a liquid phase. The liquid phase is plasma, which includes acids, lipids, dissolved electrolytes, and proteins. One particular protein suspended in the liquid phase is fibrinogen. When bleeding occurs, the fibrinogen reacts with water and thrombin (an enzyme) to form fibrin, which is insoluble in blood and polymerizes to form clots.
In a wide variety of circumstances, animals, including humans, can suffer from bleeding due to wounds or during surgical procedures. In some circumstances, the bleeding is relatively minor, and normal blood clotting functions in addition to the application of simple first aid are all that is required. In other circumstances substantial bleeding can occur. These situations usually require specialized equipment and materials as well as personnel trained to administer appropriate aid.
In an effort to address the above-described problems, materials have been developed for controlling excessive bleeding. Topical bioabsorbable hemostats (TAHs) are widely used in surgical applications. TAHs encompass products based on various woven or non-woven fabrics or sponges, typically made of at least partially resorbable materials, ranging from natural to synthetic polymers and combinations thereof, including lactide-glycolide based co-polymers such as Polyglactin 910, oxidized cellulose (OC), oxidized regenerated cellulose (ORC), gelatin, collagen, chitin, chitosan, etc. To improve the hemostatic performance, scaffolds based on the above materials can be combined with biologically-derived clotting factors, such as thrombin and/or fibrinogen.
A number of hemostatic formulations currently available on the market or in development utilize lyophilized fibrinogen, frequently in combination with lyophilized thrombin, with hemostatic formulations applied in the form of dry powder, semi-liquid paste, liquid formulation, or optionally disposed on a supporting scaffold such as bioabsorbable fabric scaffold.
For the hemostatic patches or pads containing lyophilized thrombin and fibrinogen on bioabsorbable scaffolds, there is a need to improve device performance and properties, with particularly needed enhancements related to improved wettability of the pads, leading to faster reconstitution of the lyophilized proteins, and faster hemostasis; reduced friability, i.e. reduced shedding of active powders during handling and/or cutting of the pads; and improved tissue adhesion and wound sealing properties.
U.S. Pat. No. 7,320,962 entitled “Hemoactive compositions and methods for their manufacture and use”, discloses a dried hemoactive material for inhibiting bleeding or delivering an agent, comprising: a cross-linked biologically compatible polymer which forms a hydrogel when exposed to blood; and a non-cross-linked biologically compatible polymer which solubilizes when exposed to blood: wherein the cross-linked polymer is dispersed in a dried matrix of the non-cross-linked polymer. The reference further discloses a plasticizer present in at least the non-cross-linked polymer and teaches that the plasticizer is selected from the group consisting of polyethylene glycol, sorbitol, and glycerol.
U.S. Pat. No. 6,706,690 entitled “Hemoactive compositions and methods for their manufacture and use”, discloses a dried material which forms a hydrogel when exposed to blood, said material comprising: a cross-linked biologically compatible polymer which forms a hydrogel when exposed to blood; a non-cross-linked biologically compatible polymer which dissolves when exposed to blood; a plasticizer present in the non-cross-linked biologically compatible polymer; and wherein the cross-linked polymer is dispersed in a dried matrix of the non-cross-linked polymer, wherein the non-cross-linked biologically compatible polymer dissolves in 15 minutes or less when exposed to blood. The reference further discloses a plasticizer present in the non-cross-linked polymer at from 1 weight % to 20 weight % of the material, and teaches that the plasticizer is selected from the group consisting of polyethylene glycol, sorbitol, and glycerol.
U.S. Patent Application No. 2011/0071499A1 entitled “FREE-STANDING BIODEGRADABLE PATCH”, discloses a device comprising: a film comprising a mixture of solid fibrinogen and solid thrombin, wherein the film is free-standing and is configured to form a fibrin patch upon exposure to moisture and further teaches that the film further comprises a plasticizer. It further discloses the device wherein the film comprises about 5 to about 30 weight percent polyethylene glycol.
U.S. Patent Application No. 2009/0053288A1 entitled “Hemostatic woven fabric” discloses a woven fabric having a modified crowsfoot weave pattern, further comprising a hemostatic agent. The reference further discloses the woven fabric further comprising a preservative selected from the group consisting of glycerol, propanediol, polyoxyethylene glycol (PEG), trehalose, and combinations thereof.
U.S. Patent Application No. 2007/0160653A1 entitled “Hemostatic textile” discloses a hemostatic textile, comprising: a material comprising glass fibers and one or more secondary fibers selected from the group consisting of silk fibers; polyester fibers; nylon fibers; ceramic fibers; raw or regenerated bamboo fibers; cotton fibers; rayon fibers; linen fibers; lactide and/or glycolide polymers; lactide/glycolide copolymers; thrombin or a fraction containing thrombin; and one or more hemostatic agents selected from the group consisting of RL platelets, RL blood cells; fibrin, and fibrinogen; said hemostatic textile capable of activating hemostatic systems in the body when applied to a wound. The reference further discloses the hemostatic textile further comprising a preservative selected from the group consisting of glycerol, propanediol, polyoxyethylene glycol (PEG), trehalose, and combinations thereof.
PCT Patent Publication No. WO 1997028832 A1 entitled “COMPOSITION FOR SEALING WOUNDS” discloses a hemostatic bandage contains powdered fibrinogen and thrombin adhered to a fibrous matrix with a viscous, nonaqueous adhesive such as a viscous polysaccharide, glycol, or petroleum jelly. The nonaqueous adhesive does not allow a hydrolytic reaction to occur between the fibrinogen and thrombin until the bandage is moistened by a body fluid, such as blood and teaches that the bandage can be prepared and stored for prolonged periods while retaining hemostatic activity. The reference further discloses a composition for decreasing a flow of blood from a wound, comprising: a carrier; coagulation constituents adhered to the carrier by an adhesive selected from the group consisting of water at a pH at which thrombin and fibrinogen do not interact to form fibrin, and a viscous nonaqueous biocompatible adhesive, the coagulation constituents being present in a therapeutically sufficient amount to clot and decrease the flow of blood from the wound when the composition contacts body fluids that activate clotting. The reference further discloses the composition wherein the adhesive is a nonaqueous liquid at 20° C. that adheres the coagulation constituents to the carrier. The reference further discloses the composition, wherein the nonaqueous adhesive is selected from the group consisting of propylene glycol, glycerol, petroleum jelly and polyethylene glycol.
The reference further teaches a hemostatic wound dressing, comprising: a fibrous matrix suitable for placement as a pad applied over or inserted into an open, bleeding wound; a mixture of intermingled particles of powdered coagulation factors present on the surface of the matrix, the particles being in sufficiently close contact with each other to form a clot when exposed to an aqueous medium at a physiological pH, the particles being adhered to the matrix by a viscous nonaqueous adhesive, having a viscosity of at least 100 centipoise at 20° C., that inhibits a clotting reaction between the intermingled particles until the particles are exposed to an aqueous medium at physiological pH.
The reference further discloses a hemostatic wound dressing, comprising: a fibrous matrix suitable for placement as a pad applied over or inserted into an open, bleeding wound; a mixture of intermingled particles of powdered coagulation factors present throughout the matrix, in sufficiently close contact to form a clot when exposed to an aqueous medium at a physiological pH, the particles being adhered to the matrix by a viscous nonaqueous adhesive that inhibits a clotting reaction between the intermingled particles until the particles are exposed to an aqueous medium at physiological pH, wherein the adhesive is selected from the group consisting of a polysaccharide, polyethylene glycol, propylene glycol, glycerol, and petroleum jelly, which adhesive has been applied to the matrix in a liquid form comprising less than 3% by weight water.